This proposal covers thin section, freeze-fracture and novel immunocytochemical studies of two murine models of virus induced demyelination. Infection with mouse hepatitis virus, JHM strain, causes demyelination secondary to virus induced lysis of oligodendrocytes. Large demyelinated lesions are rapidly remyelinated between 4-8 weeks post-infection. Infection with Theiler's mouse encephalomyelitis virus (TMEV), DA strain, causes an acute polio encephalomyelitis followed by a chronic relapsing demyelinating disease. The latter disease is associated with an immune mediated mechanism possibly directed against persistently infected oligodendrocytes. Remyelination is variable and often delayed, abortive or incomplete. A recently devised treatment with subcutaneous injections of an emulsification containing myelin basic protein and galactocerebroside results in consistent remyelination. These two viral infections encompass two very different mechanisms of demyelination. Comparison of perturbations in glial and axonal membrane specializations will permit better delineation of the role of membrane events in demyelination. Using newly derived freeze-fracture immunocytochemical techniques that permit unique exposures of membrane and viral antigens, we will be able to compare the location of viral antigens within infected oligodencytes with respect to normal glial and axonal membrane specializations. Additionally, these techniques will permit ultrastructural localization of endogenous IgG, macrophages and B & T cell subsets to specific sites along demyelinated or remyelinated fibers. The precision in this localization is a qualitative leap in improvement over previous crude localization studies. Instead of simply describing what immune and viral elements are contained within lesions, these techniques will help elucidate the molecular mechanism of demyelination by permitting definition of the exact membrane sites where these components interact.